Previous studies show that the divergent paradigms of endurance exercise training, caloric restriction, and experimentally-induced hypertension (pressure overload) share a common adaptive response by inducing down regulation of the high ATPase alphamyosin heavy chain (MHC) and concomitant up regulation f the low ATPase, beta MHC. Also, cardiac genes encoded for alpha and beta MHCs have been shown to be chiefly regulated via transcriptional processes involving thyroid hormone receptor (TR) interaction (binding) with segments of DNA designated as thyroid response elements (TRE) in the two genes. The primary goal of this proposal is to perform studies to test the general hypothesis that the down regulation of alpha MHC gene expression in the above paradigms is mediated through a common mechanism involving reduced regulatory control of thyroid hormone on the alpha MHC gene. To test this hypothesis, we will use the separate and combined models of food restriction and pressure overload, along with appropriate control groups, to study the following processes: 1) the relative content of TR isoforms (mRNA and protein) in cardiac tissue, and the capacity of the TR pool to bind labeled triiodothyronine (T3) using Scatchard analyses; 2) the ability of the TR pool of nuclear extracts of cardiac tissue to interact with TREs of the alpha MHC gene using gel mobility shift assays; 3) the ability of nuclear extracts containing putative thyroid receptor auxiliary protein (TRAP) factors to modify interactions of synthetic TRs with the TRE of the alpha MHC gene; 4) the ability of elevations in carbohydrate metabolism to up regulate alpha MHC in the above models via alteration in levels of TRs and/or TRAP factors. Collectively, these experiments will more clearly delineate the role of subcellular T3 function and of carbohydrate metabolism in the control of cardiac isomyosin adaptation in response to both altered mechanical and metabolic interventions.